The OPTIMIZE patient- and family-centered, primary care-based deprescribing intervention for older adults with dementia or mild cognitive impairment and multiple chronic conditions: study protocol for a pragmatic cluster randomized controlled trial.

BACKGROUND: Most individuals with dementia or mild cognitive impairment (MCI) have multiple chronic conditions (MCC). The combination leads to multiple medications and complex medication regimens and is associated with increased risk for significant treatment burden, adverse drug events, cognitive changes, hospitalization, and mortality. Optimizing medications through deprescribing (the process of reducing or stopping the use of inappropriate medications or medications unlikely to be beneficial) may improve outcomes for MCC patients with dementia or MCI. METHODS: With input from patients, family members, and clinicians, we developed and piloted a patient-centered, pragmatic intervention (OPTIMIZE) to educate and activate patients, family members, and primary care clinicians about deprescribing as part of optimal medication management for older adults with dementia or MCI and MCC. The clinic-based intervention targets patients on 5 or more medications, their family members, and their primary care clinicians using a pragmatic, cluster-randomized design at Kaiser Permanente Colorado. The intervention has two components: a patient/ family component focused on education and activation about the potential value of deprescribing, and a clinician component focused on increasing clinician awareness about options and processes for deprescribing. Primary outcomes are total number of chronic medications and total number of potentially inappropriate medications (PIMs). We estimate that approximately 2400 patients across 9 clinics will receive the intervention. A comparable number of patients from 9 other clinics will serve as wait-list controls. We have > 80% power to detect an average decrease of - 0.70 (< 1 medication). Secondary outcomes include the number of PIM starts, dose reductions for selected PIMs (benzodiazepines, opiates, and antipsychotics), rates of adverse drug events (falls, hemorrhagic events, and hypoglycemic events), ability to perform activities of daily living, and skilled nursing facility, hospital, and emergency department admissions. DISCUSSION: The OPTIMIZE trial will examine whether a primary care-based, patient- and family-centered intervention educating patients, family members, and clinicians about deprescribing reduces numbers of chronic medications and PIMs for older adults with dementia or MCI and MCC. TRIAL REGISTRATION: NCT03984396. Registered on 13 June 2019.

Better Respiratory Education and Treatment Help Empower (BREATHE) study: Methodology and baseline characteristics of a randomized controlled trial testing a transitional care program to improve patient-centered care delivery among chronic obstructive pulmonary disease patients.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of hospitalizations. Interventional studies focusing on the hospital-to-home transition for COPD patients are few. In the BREATHE (Better Respiratory Education and Treatment Help Empower) study, we developed and tested a patient and family-centered transitional care program that helps prepare hospitalized COPD patients and their family caregivers to manage COPD at home. METHODS: In the study's initial phase, we co-developed the BREATHE transitional care program with COPD patients, family-caregivers, and stakeholders. The program offers tailored services to address individual patients' needs and priorities at the hospital and for 3months post discharge. We tested the program in a single-blinded RCT with 240 COPD patients who were randomized to receive the program or 'usual care'. Program participants were offered the opportunity to invite a family caregiver, if available, to enroll with them into the study. The primary outcomes were the combined number of COPD-related hospitalizations and Emergency Department (ED) visits per participant at 6months post discharge, and the change in health-related quality of life over the 6months study period. Other measures include 'all cause' hospitalizations and ED visits; patient activation; self-efficacy; and, self-care behaviors. DISCUSSION: Unlike 1month transitional care programs that focus on patients' post-acute care needs, the BREATHE program helps hospitalized COPD patients manage the post discharge period as well as prepare them for long term self-management of COPD. If proven effective, this program may offer a timely solution for hospitals in their attempts to reduce COPD rehospitalizations.

The complete genome of a baculovirus isolated from an insect of medical interest: Lonomia obliqua (Lepidoptera: Saturniidae).

Lonomia obliqua (Lepidoptera: Saturniidae) is a species of medical importance due to the severity of reactions caused by accidental contact with the caterpillar bristles. Several natural pathogens have been identified in L. obliqua, and among them the baculovirus Lonomia obliqua multiple nucleopolyhedrovirus (LoobMNPV). The complete genome of LoobMNPV was sequenced and shown to have 120,022 bp long with 134 putative open reading frames (ORFs). Phylogenetic analysis of the LoobMNPV genome showed that it belongs to Alphabaculovirus group I (lepidopteran-infective NPV). A total of 12 unique ORFs were identified with no homologs in other sequenced baculovirus genomes. One of these, the predicted protein encoded by loob035, showed significant identity to an eukaryotic transcription terminator factor (TTF2) from the Lepidoptera Danaus plexippus, suggesting an independent acquisition through horizontal gene transfer. Homologs of cathepsin and chitinase genes, which are involved in host integument liquefaction and viral spread, were not found in this genome. As L. obliqua presents a gregarious behavior during the larvae stage the impact of this deletion might be neglectable.

Evaluation of tolerability and ability to increase immunosuppression in renal transplant patients converted from mycophenolate mofetil to enteric-coated mycophenolate sodium.

BACKGROUND: Dose reductions or discontinuations of mycophenolate mofetil (MMF) result in higher incidences of acute rejection and graft loss. Converting renal transplant patients experiencing MMF-related gastrointestinal (GI) side effects to equimolar enteric-coated mycophenolate sodium (EC-MPS) may relieve GI symptoms. METHODS: In this prospective 12-month study, renal transplant patients maintained on suboptimal MMF doses (<1500 mg/d) due to GI intolerance were converted to equimolar EC-MPS followed by incremental EC-MPS dose increases (180 mg/d) every 7 weeks to an established maximum, if well tolerated. Changes in GI symptoms were assessed by physician judgment and Gastrointestinal Symptom Rating Scale (GSRS). RESULTS: Twenty-five patients (mean age: 52.0 +/- 13.6 years) were converted from MMF (930.0 +/- 153.4 mg/d) to equimolar EC-MPS (669.6 +/- 110.5 mg/d) at day 0. Twenty-three of 25 patients tolerated equimolar dose conversion and one or more EC-MPS dose increments at week 28. Compared to baseline, patients received significantly more EC-MPS at week 28 and week 49 (mean dose: 1033.0 +/- 164.8 mg/d, P < .0001 and 1001.7 +/- 209.0 mg/d, P < .0001, respectively). Two patients dropped out by week 7 for reasons unrelated to EC-MPS. The mean serum creatinine remained stable and no clinical acute rejection episodes occurred over 12 months. Mean GSRS total score remained stable through month 12 when compared to day 0 despite increases in EC-MPS dose. CONCLUSION: In renal transplant patients receiving suboptimal MMF doses due to GI symptoms, conversion to EC-MPS enabled equimolar prescription and subsequent dose increase without increased GI intolerance.

Supporting self-management for patients with complex medical needs: recommendations of a working group.

Increasing numbers of persons live with complex chronic medical needs and are at risk for poor health outcomes. These patients require unique self-management support, as they must manage many, often interacting, tasks. As part of a conference on Managing Complexity in Chronic Care sponsored by the Department of Veterans Affairs, a working group was convened to consider self-management issues specific to complex chronic care. In this paper, we assess gaps in current knowledge on self-management support relevant to this population, report on the recommendations of our working group, and discuss directions for future study. We conclude that this population requires specialized, multidimensional self-management support to achieve a range of patient-centred goals. New technologies and models of care delivery may provide opportunities to develop this support. Validation and quantification of these processes will require the development of performance measures that reflect the needs of this population, and research to prove effectiveness.

Identification and characterization of the Spodoptera littoralis nucleopolyhedrovirus type B lef-3 gene.

We have identified a gene from the Spodoptera littoralis nucleopolyhedrovirus type B (SpliNPV-B) with several characteristics that suggest that it is homologous to the lef-3 genes of the Autographa californica and Orgyia pseudotsugata NPVs (AcMNPV and OpMNPV, respectively). The SpliNPV-B lef-3 gene was mapped between 43.6 and 45.5 map units of the SpliNPV-B genome. Northern blot analysis showed that SpliNPV-B lef-3 was expressed as a 1.6 Kb transcript at 5 h post infection (p.i.), reached high levels at 24 h p.i., and remained highly expressed at 56 h p.i. Transcription of SpliNPV-B lef-3 initiated at two distinct sites downstream from a TATA-box motif and terminated 25 nucleotides downstream from the translation stop site of the putative LEF-3 polypeptide. The 5'-boundaries of lef-3 promoter elements were investigated by transient expression assays, which revealed that the major components of the lef-3 promoter are within a 183 base pair region upstream of the distal transcription initiation site. Transfection of SpliNPV-B infected Sf9 cells with anti-sense oligonucleotides designed to inhibit LEF-3 expression resulted in substantial reduction of viral DNA replication, suggesting that the role of SpliNPV-B lef-3 may be similar to that of AcMNPV and OpMNPV lef-3 genes, which are essential for viral DNA replication.

Economic analysis of Neoral in de novo renal transplant patients in Canada.

This pilot economic evaluation was performed as part of the Canadian arm of an international randomized, controlled, double-blind safety and tolerability trial (OLM-105/NOF-2). The clinical study compared the safety and tolerability of a new microemulsion oral formulation of cyclosporine A (Neoral) with the oral cyclosporine. A preparation currently in use (Sandimmune SGC)/(SGC). To assess the economic impact of Neoral in newly grafted renal transplant patients, primary cost data were collected at the five participating Canadian centers and evaluated from the Ministry of Health (MOH) and hospital perspectives. The results of this cost analysis are presented in this paper. Since the new formulation has shown more consistent absorption and a more predictable pharmacokinetic profile, medical resource utilization and, consequently, cost of treatment could be expected to be lower for those renal transplant recipients treated with Neoral than for those receiving standard SGC. The findings of this study support this hypothesis. Robustness of the conclusion was confirmed with sensitivity analyses. Reduced health care costs for patients treated with Neoral were primarily a result of fewer hospitalization days and lower physician costs for inpatient and outpatient procedures.

[Osteonecrosis of the femoral head. MRI study of 60 cases]. / L'ostéonécrose de la tête fémorale. Etude par IRM de 60 cas.

Normal and pathologic femoral heads have been studied by MRI at 1.5 Tesla. The study was centered upon avascular necrosis (53 lesions). Twenty normal subjects and three patients with algodystrophy were examined. The osteonecrosis patterns were established from known lesions. A low signal rim surrounds an upper polar zone of conserved (Type I) or decreased (Type II) signal. The lesions age correlates significantly with their type: amongst type I lesions, 6 are asymptomatic and the 21 others have a mean age of 5.5 months; Type II lesions have a mean age of 12.7 months. Fourteen lesions were not seen on plain radiographs and six were not detected by bone scan. The older lesions with femoral head deformation are better depicted by standard radiologic techniques. Conservatively MRI is the most efficient examination for recent avascular necrosis lesions.

Evaluating the acquisition of colposcopy skills in an obstetric-gynecologic residency program.

Instruction in colposcopic technique is now an integral component of residency training in obstetrics and gynecology. No statistical method for assessing colposcopy skills has been reported on before. The statistical calculations of sensitivity, specificity and kappa were applied to determine if there was any progressive acquisition of colposcopy skills by the colposcopy trainee during the four-year residency program.